Intracranial aneurysm management in patients with late-onset Pompe disease (LOPD)

Neurological Sciences - Pompe disease is a rare hereditary metabolic disorder caused by α-glucosidase (GAA) deficiency. The late-onset form of the disease (LOPD) is considered a multisystemic...     

Cerebromeningeal hemorrhage. Analysis of autopsies performed over a 10-year period

A study was conducted on the medical records of 353 patients who died of a subarachnoid hemorrhage (SAH) and who were submitted to autopsy over the last 10 years. SAH was associated with arterial hypertension in 180 (51%) cases, with ruptured aneurysms in 102 (28.9%), and with other pathologies in 71 (20.1%). The patients with hemorrhage associated with arterial hypertension were mostly males, and those with hemorrhage due to aneurysms were mostly females. Of the patients with aneurysms, 36 (35.3%) had aneurysms in the anterior communicating artery, 30 (29.4%) in the internal carotid artery, and 23 (22.6%) in the middle cerebral artery. Among the patients with aneurysms who suffered rebleeding and vasospasm, 59.1% and 61.5%, respectively, were classified as grade I and II upon admission, and all evolved toward grade IV after these complications. Vasospasm predominated from the 3rd to the 10th day after hemorrhage, and rebleeding from the 9 to 16th day and both were most frequent among patients with aneurysms of the anterior communicant artery. Sixty eight percent of the patients with aneurysms died during the first 9 days after hemorrhage. Because of our conduct was to operate systematically late, a considerable number of patients lost the opportunity to be treated surgically with possible favorable evolution due to vasospasm or rebleeding.     

Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review

BACKGROUND AND AIM: In patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing hepatocellular carcinoma (HCC) has never been systematically assessed, and present systematic review was aimed at this issue. METHODS: Pertinent cross-sectional studies having as a reference standard pathological examinations of the explanted liver or resected segment(s), biopsies of focal lesion(s), and/or a period of follow-up, were identified using MEDLINE, EMBASE, Cochrane Library, and CancerLit. Pooled sensitivity, specificity, and likelihood ratios (LR) were calculated using the random effect model. Summary receiver operating characteristic (SROC) curve and predefined subgroup analyses were made when indicated. RESULTS: The pooled estimates of the 14 US studies were 60% (95% CI 44-76) for sensitivity, 97% (95% CI 95-98) for specificity, 18 (95% CI 8-37) for LR+, and 0.5 (95% CI 0.4-0.6) for LR-; for the 10 CT studies sensitivity was 68% (95% CI 55-80), specificity 93% (95% CI 89-96), LR+ 6 (95% CI 3-12),and LR- 0.4 (95% CI 0.3-0.6); for the nine MRI studies sensitivity was 81% (95% CI 70-91), specificity 85% (95%CI 77-93), LR+ 3.9 (95%CI 2-7), and LR- 0.3 (95% CI 0.2-0.5). The sensitivity and specificity of AFP varied widely, and this could not be entirely attributed to the threshold effect of the different cutoff levels used. CONCLUSIONS: US is highly specific but insufficiently sensitive to detect HCC in many cirrhotics or to support an effective surveillance program. The operative characteristics of CT are comparable, whereas MRI is more sensitive. High-quality prospective studies are needed to define the actual diagnostic role of AFP.     

Hypothalamic dysfunction is related to sleep impairment and CSF biomarkers in Alzheimer’s disease

Hypothalamus is a key brain region regulating several essential homeostatic functions, including the sleep–wake cycle. Alzheimer’s disease (AD) pathology affects nuclei controlling sleep–wake rhythm sited in this brain area. Since only post-mortem studies documented the relationship between hypothalamic atrophy and sleep–wake cycle impairment, we investigated in AD patients the possible hypothalamic in vivo alteration using 2-deoxy-2-(18F) fluoro-d-glucose ([18F]FDG) positron emission tomography ([18F]FDG PET), and its correlations with sleep impairment and cerebrospinal-fluid (CSF) AD biomarkers (tau proteins and β-amyloid₄₂). We measured sleep by polysomnography, CSF AD biomarkers and orexin levels, and hypothalamic [18F]FDG PET uptake in a population of AD patients compared to age- and sex-matched controls. We documented the significant reduction of hypothalamic [18F]FDG PET uptake in AD patients (n = 18) compared to controls (n = 18) (p < 0.01). Moreover, we found the increase of CSF orexin levels coupled with the marked alteration of nocturnal sleep in AD patients than controls. We observed the significant association linking the reduction of both sleep efficiency and REM sleep to the reduction of hypothalamic [18F]FDG PET uptake in the AD group, which in turn negatively correlated with the total-tau/beta-amyloid₄₂ ratio (index of more marked neurodegeneration). Moreover, controls but not AD patients showed [18F]FDG PET interconnections between hypothalamus and limbic system. We documented the in vivo dysfunction of hypothalamus in AD patients, which lost the physiological connections with limbic system and was correlated with both nocturnal sleep disruption and CSF AD biomarkers.     

The role of acid and alkaline reflux in laryngeal squamous cell carcinoma

HYPOTHESIS: At present, main factors considered responsible for the onset of squamous cell carcinoma are tobacco smoking, alcohol abuse, and exposure to viral and toxic agents. In last years, great interest has been focused on gastroesophageal reflux as independent carcinogenic factor and co-carcinogen in association with smoking and alcohol assumption. STUDY DESIGN: Initially, the aim of this study was to objectively evaluate the presence of distal and proximal esophageal reflux with multielectrode pH measurement in patients with cancer of the larynx and/or hypopharynx (group A). However, in the course of the study, pharyngolaryngeal cancer was also observed in 4 patients with achlorhydria; therefore, the hypothesis that alkaline reflux might be involved in the onset of laryngeal cancer was tested (group B). METHODS: Twenty-one consecutive patients with laryngeal or hypopharyngolaryngeal squamous cell carcinoma (group A) entered the study. Twenty-one patients without laryngo-pharyngeal diseases were used as control subjects. A validated questionnaire of the clinical history was completed by all patients who underwent 24-hour pH monitoring. Group B included 40 consecutive gastrectomized patients (28 males and 12 females) in whom biliary or alkaline reflux was directly consequent to Billroth I or Billroth II operation. The control group was composed of 40 non-gastrectomized dyspeptic patients. The clinical history was controlled and obtained; EDGS and ENT examination with videolaryngoscopy was performed in all patients. RESULTS: In group A, pH measurement showed pathological reflux in 80.9% (17 of 21) of patients with no typical symptoms in 63.7% of them. The difference was significant with respect to the control group. In group B, 6 of 40 (15%) had preneoplastic lesions or a history of laryngeal tumor. The difference was significant with respect to the control group. A total of 7.5% of group B patients had previously undergone CO2 laser cordectomy for laryngeal squamous cell carcinoma and 7.5% had leukoplakia. We found a significantly higher incidence (<.05) of neoplastic and preneoplastic disease of the larynx in patients undergoing Billroth II and total gastrectomy than in those undergoing Billroth I and Roux-en-Y resection. We also found a significant increase (<.01) in ENT lesions in the group of patients who had undergone gastrectomy more than 20 years previously. CONCLUSIONS: In agreement with literature reports, results obtained in group A confirmed that gastroesophageal reflux is often present in patients with neoplastic lesions of the pharynx and larynx. Furthermore, gastric resection is indicated for the first time as an additional risk factor or cofactor of precancerosis and squamous cell carcinoma of the pharynx or larynx. Further studies are necessary to establish the cause and effect relationship between biliary reflux and pharyngo-laryngeal tumors.     

Radiofrequency thermal ablation of liver tumors

Radiofrequency ablation (RFA) of liver tumors was first proposed in 1990. New technologies enable us to produce liver thermal lesions of approximately 3–3.5 cm in diameter; RFA has consequently become an emerging percutaneous therapeutic option both for small hepatocellular carcinoma (HCC) and for non-resectable liver metastases, mainly from colorectal cancer. New devices (for example, triplet of cooled needles, wet needles) and combined therapies (tumor ischemia and RFA) have made it possible to treat large tumors. RFA can be carried out by a percutaneous, laparoscopic or laparotomic approach. Percutaneous RFA can be performed with local anaesthesia and mild sedation; deep sedation or general anaesthesia are also used. The guidance system is generally represented by ultrasound. CT or MR examinations are the more sensitive tests for assessing therapeutic results. The series of patients treated with RFA allow the technique to be considered as effective and safe, achieving a relatively high rate of cure in properly selected cases; it should be classified as curative/effective treatment for HCC, replacing percutaneous ethanol injection. The complication rate of RFA is low but not negligible; key elements in a strategy to minimize them are identified.     

Pleiotrophin expression in astrocytic and oligodendroglial tumors and it’s correlation with histological diagnosis,microvascular density,cellular proliferation and overall survival

BACKGROUND: Pleiotrophin (PTN) is a secreted cytokine with several properties related with tumor development, including differentiation, angiogenesis, invasion, apoptosis and metastasis. There is evidence that PTN has also a relevant role in primary brain neoplasms and its inactivation could be important to treatment response. Astrocytic and oligodendroglial tumors are the most frequent primary brain neoplasms. Astrocytic tumors are classified as pilocytic astrocytoma (PA), diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GBM). Oligodendroglial tumors are classified as oligodendroglioma (O) and anaplastic oligodendroglioma (AO). The aim of the present study was to compare PTN expression, in astrocytomas and oligodendrogliomas and its association with the histological diagnosis, microvascular density, proliferate potential and clinical outcome. METHODS: Seventy-eight central nervous system tumors were analyzed. The histological diagnosis in accordance with WHO classification was: 13PA, 18DA, 8AA, 15GBM, 16O and 8AO. Immunohistochemistry was realized with these specific antibodies: pleiotrophin, CD31 to microvascular density and Ki-67 to cell proliferation. RESULTS: PTN expression was significantly higher in GBM and AA when compared to PA and higher in GBM compared to DA. PTN expression did not differ between O and AO. Proliferate index and microvascular density were evaluated only in high grade tumors (AA, GBM and AO) divided in three groups according to PTN expression (low, intermediate and high). These results showed no statistical difference between PTN expression and index of cellular proliferation and neither to PTN expression and microvascular density. Overall survival (OS) analysis (months) showed similar results in high grade gliomas with different levels of PTN expression. CONCLUSIONS: Our results suggest that PTN expression is associated with histopathological grade of astrocytomas. Proliferation rate, microvascular density and overall survival do not seem to be associated with PTN expression.     

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid

Introduction

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5–8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of ¹⁸F-DOPA PET/CT in patients with recurrent MTC.

Materials and methods

60 patients (mean age 64?±?13 years, range 44–82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging ¹⁸F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21?±?11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of ¹⁸F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan–Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis.

Results

¹⁸F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p?=?0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p?=?0.04). ¹⁸F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p?<?0.001 and p?=?0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC.

Conclusion

¹⁸F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

     

Prostacyclin-lipoprotein interactions. Studies on human platelet aggregation and adenylate cyclase

The in vitro effects of different lipoprotein fractions (VLDL, LDL and HDL) on human washed platelet aggregation, induced by collagen and thrombin, were evaluated in the presence and absence of PGI2. Although VLDL and LDL increased the platelet aggregation while HDL showed an opposite effect, none of the tested lipoprotein fractions affected the potency of PGI2 as inhibitor of platelet aggregation (IC50). In addition, studies were performed to evaluate the effects of lipoproteins on adenylate cyclase activity in human platelet membranes. The three lipoprotein classes inhibited both basal and PGI2-stimulated adenylate cyclase without affecting the EC50 for PGI2. This inhibitory activity was not specifically elicited by any protein or lipid since neither bovine serum albumin nor a lipid emulsion (Intralipid) displayed any inhibition. The effect on adenylate cyclase elicited by VLDL, LDL and HDL does not seem to be correlated with the activity on platelet aggregation. It is concluded that mediators other than cAMP might be involved in the control of platelet function by lipoproteins.